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A drug that may combat the addictive — and sometimes fatal — effects of cocaine could be available for human clinical trials within the next three years, according to researchers at Johns Hopkins University who have been studying the drug in mice.

Called CGP3466B or Omigapil, the compound was originally developed to treat neurological diseases, but scientists are now testing its effectiveness in rodents as a way to combat cocaine addiction and overdoses.

“At present, there are no FDA-approved medications for cocaine addiction,” said Joni L. Rutter, PhD, a director at the National Institute on Drug Abuse who was not involved with the study, in an email. There were about 2 million cocaine and crack cocaine users in the United States in 2008, according to the most recent statistics from the National Survey on Drug Use and Health.

“These findings are important contributions to our understanding of cocaine's actions, and provide a rationale for generating and testing new compounds for treating cocaine addiction,” Dr. Rutter added.

Cocaine: A Long History of Use and Addiction

Cocaine has been around for a long time. In South America, people still chew it in its less potent form, cocoa leaves, as a mild stimulant. In the early 1900s, American doctors prescribed cocaine as medication for a variety of ailments, according to Ben Cort, a spokesman at the Center for Dependency, Addiction and Rehabilitation at University of Colorado Hospital and a former cocaine addict.

However, it wasn’t until the 1970s and '80s that cocaine became a popular recreational drug in the United States, Cort added. It’s taken even longer for cocaine addiction to be recognized as a medical malady. Some researchers say there's still a lot of misunderstanding about cocaine addiction in particular, and drug addiction in general.

“For a long time addiction was viewed as some sort of moral weakness. People didn’t view it as a disease process,” said Risheng Xu, a neuroscience student at Johns Hopkins School of Medicine and author on the study.

“People have been using cocaine for a long time, but, until now, we didn’t have a very good understanding of how cocaine worked at the molecular level,” he added. “Without that, you can’t do anything about it [cocaine addiction].”

How Cocaine Addiction Works

The Johns Hopkins' study, published in the journal Neuron, addresses the nitty-gritty science behind cocaine addiction, which centers around a brain protein called GAPDH. It’s an intimidating name, but the protein simply aids metabolism. When cocaine enters the body it tells the brain to create the gas nitric oxide, and the nitric oxide immediately attaches to GAPDH. This creates an almost instant rush that's highly addictive.

“Cocaine is a very fast and very intense high. It hits you hard, and it hits you fast, and it leaves you wanting more quickly,” Cort said.

"Addiction develops very quickly," he added. "It just wakes up something in your brain that was there and wanted to get out anyway."

GAPDH is also the protein that helps initiate brain cell death when people overdose on cocaine. To help addicts overcome their drug addictions and prevent cell death, the Johns Hopkins scientists realized they needed to keep GAPDH and nitric oxide from binding. Rather than inventing a new compound that would do this, the researchers injected mice with a drug called Omigapil, which was originally developed to treat amyotrophic lateral sclerosis (ALS) but did not work for that purpose.

Omigapil also likes to bind to GAPDH, and it binds so well and so tightly that the nitric oxide can’t take hold.

In theory, this seemed like a great idea, but the researchers didn't know if it would work in practice. To see if Omigapil was doing what they hoped, they did two sets of experiments — one looking at the addictive effects of cocaine and the other analyzing its toxic effects.

Xu used mice to model cocaine addiction. The researcher put a mouse in a box that had two rooms. Xu gave the mouse cocaine only when it was in one of the two rooms. Over time, the mouse began to associate that specific room with a cocaine high and tended to hang out there.

“It’s kind of like you’re living in your house, and you always get fed in the kitchen, and at some point you’re like, ‘If I’m hungry I’m going to go to the kitchen. Food always comes from the kitchen,’” Xu said.

When they gave the mouse Omigapil, it spent about 80 percent less time in the cocaine room, suggesting that it weren't experiencing as many addiction cravings, Xu said. This is important because it means doctors could potentially give this drug to humans to help them get through drug rehabilitation.

"I work in a treatment center and I see this all day, every day," Cort said. "It’s a very difficult habit for people to kick. It’s a very hard thing to stop."

The researchers also analyzed brain damage caused by lethal doses of cocaine. Cocaine overdoses can create massive cell death within the brain. However, mice who were immediately given Omigapil after overdosing on cocaine saw a significant decrease in cell death.

While Omigapil worked well in mice, that doesn’t mean it’ll be effective in people.

“The weakness for the study is you wonder whether the mouse model for the cocaine addiction is going to be the same — is that model directly applicable for humans?” Xu said. “You don’t know.”

In the next two to three years, Xu said, Omigapil will go through Phase II trials to determine its efficacy in humans. If it works as well in people as it did in mice, the compound could become a viable treatment option for addiction.

“[Cocaine] is extremely addictive,” Cort commented. “I think it would be exciting to know a drug that could work to curb cocaine addiction.”

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